@article{01405ddc3c4e4054b6851ad70ad0e17e,
title = "Whole-genome reconstruction and mutational signatures in gastric cancer",
abstract = "BACKGROUND: Gastric cancer is the second highest cause of global cancer mortality. To explore the complete repertoire of somatic alterations in gastric cancer, we combined massively parallel short read and DNA paired-end tag sequencing to present the first whole-genome analysis of two gastric adenocarcinomas, one with chromosomal instability and the other with microsatellite instability.RESULTS: Integrative analysis and de novo assemblies revealed the architecture of a wild-type KRAS amplification, a common driver event in gastric cancer. We discovered three distinct mutational signatures in gastric cancer--against a genome-wide backdrop of oxidative and microsatellite instability-related mutational signatures, we identified the first exome-specific mutational signature. Further characterization of the impact of these signatures by combining sequencing data from 40 complete gastric cancer exomes and targeted screening of an additional 94 independent gastric tumors uncovered ACVR2A, RPL22 and LMAN1 as recurrently mutated genes in microsatellite instability-positive gastric cancer and PAPPA as a recurrently mutated gene in TP53 wild-type gastric cancer.CONCLUSIONS: These results highlight how whole-genome cancer sequencing can uncover information relevant to tissue-specific carcinogenesis that would otherwise be missed from exome-sequencing data.",
author = "Niranjan Nagarajan and Denis Bertrand and Hillmer, {Axel M.} and Zang, {Zhi Jiang} and Fei Yao and Jacques, {Pierre Etienne} and Teo, {Audrey S M} and Ioanna Cutcutache and Zhenshui Zhang and Lee, {Wah Heng} and Sia, {Yee Yen} and Song Gao and Ariyaratne, {Pramila N.} and Andrea Ho and Woo, {Xing Yi} and Lavanya Veeravali and Ong, {Choon Kiat} and Niantao Deng and Desai, {Kartiki V.} and Khor, {Chiea Chuen} and Hibberd, {Martin L.} and Atif Shahab and Jaideepraj Rao and Mengchu Wu and Ming Teh and Feng Zhu and Chin, {Sze Yung} and Brendan Pang and So, {Jimmy B Y} and Guillaume Bourque and Richie Soong and Sung, {Wing Kin} and Teh, {Bin Tean} and Steven Rozen and Xiaoan Ruan and Yeoh, {Khay Guan} and Tan, {Patrick B O} and Yijun Ruan",
note = "Funding Information: This work was supported by the Agency for Science Technology and Research (A*STAR), Singapore, the Translational Clinical Research (TCR) Flagship Programme - {\textquoteleft}The Singapore Gastric Cancer Consortium-Improving Outcomes for Our Patients{\textquoteright}, the National Cancer Institute (USA) NCI: 5 R33 CA126996-02 (Pair-end-ditag technologies for the complete annotation of fusion genes) and funds from the Lee Foundation and the National Cancer Centre Research Foundation. Additional support was provided by the Genome Institute of Singapore internal research funds from the National Medical Research Council of Singapore and Biomedical Research Council (BMRC) of A*STAR. We thank Hwee Meng Low and Yeen Hui Choy for help on PCR validation, Herv{\'e} Thoreau for managing of the sequencing platforms, See Ting Leong, Say Chuan Neo, and Poh Sum D Choi for SOLiD sequencing and Chin Thing Ong, Adeline Lai San Chew, Kian Chew Lim, Yen Ling Yee, Thompson Poh, Raquel Peh, and Crystal Toh for Illumina sequencing.",
year = "2012",
doi = "10.1186/gb-2012-13-12-r115",
language = "English",
volume = "13",
pages = "R115",
journal = "Genome biology",
issn = "1465-6906",
publisher = "BioMed Central",
number = "12",
}